PROJECT SUMMARY Our overall goal is to improve the completion of CRC (CRC) screening tests among mid-life adults (50-64 years of age) who reside in Appalachia. CRC screening tests are widely available, however many mid-life adults do not adhere to screening guidelines. Ohio ranks 31st and Kentucky ranks 24th among the United States (U.S.) for CRC screening adherence and CRC screening among Appalachian residents is lower than national standards. This factor likely contributes to the higher CRC incidence and mortality rates in Appalachian Ohio and Appalachian Kentucky compared to rates in the U.S. Because of these CRC disparities, the Appalachian region is included in one of three ?hotspots? (spatial clusters of counties with unnecessarily high CRC mortality rates) identified in the U.S. that could benefit from CRC screening interventions. Factors contributing to CRC disparities among Appalachian residents include: lower socioeconomic status and educational attainment; limited health literacy; lifestyle factors; significant co-morbidities; health insurance issues; living in a rural area with inadequate public transportation; less access to healthcare; and lower CRC screening rates. Based on these screening data, lack of public transportation and the distance needed to travel for a colonoscopy in a rural region, and that annual CRC screening with fecal immunochemical test (FIT) is a recommended test option by the United States Preventive Service Task Force and the American Cancer Society, a mailed FIT intervention is a more viable strategy for Appalachian residents. While FIT outreach programs have been shown to increase CRC screening, many adults still do not complete a FIT mailed to their home (up to 70% non-completion in past studies). Common patient barriers to FIT completion include: lack of provider recommendation, perception of low CRC risk; concern about doing the test correctly; messiness with sample collection; concern about test results; forgetfulness; and embarrassment with specimen mailing. Importantly, many of these barriers may be addressed by materials (e.g. FIT instructions) sent with a FIT. However, a limitation of prior FIT outreach interventions has been including materials that are heavy in text and only supplemented with pictures, which may not be appropriate for individuals with limited health literacy. We will develop and pilot test two FIT outreach interventions that address this limitation and overcome other common CRC screening barriers. The interventions will use newer technology, audio or video brochures that include FIT instructions. Audio and video brochures incorporate audio or a video screen (with audio capabilities) surrounded by illustrations, pictures, and text. These brochures offer novel approaches for increasing FIT return by addressing common FIT barriers via targeted CRC screening information and FIT instructions appropriate for all health literacy skills. In addition, we will include disposable gloves in the interventions to address a common screening barrier, the perceived messiness associated with specimen collection. An established interdisciplinary team will use community-engaged research strategies to: Develop two mail- based FIT outreach interventions that use newer technology (audio brochure or video brochure) and disposable gloves in collaboration with Appalachian mid-life adults and healthcare providers (Aim 1); and Conduct a pilot study of the two developed mail-based FIT outreach interventions vs. mailed usual care materials to establish acceptability and obtain preliminary efficacy data on increasing CRC screening (Aim 2). Study findings will inform a future large randomized controlled trial to test the efficacy of the developed FIT outreach interventions.